Cited by 163Flavonoids in Medical ResearchTelomeres, Telomerase, and SenescencePhytochemicals and Antioxidant Activities

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Apigenin suppresses the senescence-associated secretory phenotype and paracrine effects on breast cancer cells

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Perrott, Kevin M., Wiley, Christopher D., Desprez, Pierre-Yves, Campisi, Judith·2017·GeroScience

DOI 10.1007/s11357-017-9970-1PMC PMC5411372

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Abstract

Apigenin (4',5,7,-trihydroxyflavone) is a flavonoid found in certain herbs, fruits, and vegetables. Apigenin can attenuate inflammation, which is associated with many chronic diseases of aging. Senescent cells-stressed cells that accumulate with age in mammals-display a pro-inflammatory senescence-associated secretory phenotype (SASP) that can drive or exacerbate several age-related pathologies, including cancer. Flavonoids, including apigenin, were recently shown to reduce the SASP of a human fibroblast strain induced to senesce by bleomycin. Here, we confirm that apigenin suppresses the SASP in three human fibroblast strains induced to senesce by ionizing radiation, constitutive MAPK (mitogen-activated protein kinase) signaling, oncogenic RAS, or replicative exhaustion. Apigenin suppressed the SASP in part by suppressing IL-1α signaling through IRAK1 and IRAK4, p38-MAPK, and NF-κB. Apigenin was particularly potent at suppressing the expression and secretion of CXCL10 (IP10), a newly identified SASP factor. Further, apigenin-mediated suppression of the SASP substantially reduced the aggressive phenotype of human breast cancer cells, as determined by cell proliferation, extracellular matrix invasion, and epithelial-mesenchymal transition. Our results support the idea that apigenin is a promising natural product for reducing the impact of senescent cells on age-related diseases such as cancer.

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Authors: Perrott, K. M., Wiley, C. D., Desprez, P.-Y., & Campisi, J.
Affiliations: Buck Institute for Research on Aging (US)
California Pacific Medical Center (US)
Corresponding author: Campisi, Judith
ORCID: Wiley, Christopher D.
Desprez, Pierre-Yves
Campisi, Judith
Venue: GeroScience
Publisher: Springer Science and Business Media LLC
Published: 2017-04
Volume: 39
Issue: 2
Pages: 161-173
ISSN: 2152-4041 (ISSN-L)
2509-2715
2509-2723
DOI: 10.1007/s11357-017-9970-1
PMC: PMC5411372
OpenAlex: W2604407819
Cited by: 163
References: 42
Citations by year: 2026: 8 · 2025: 21 · 2024: 28 · 2023: 18 · 2022: 17 · 2021: 19 · 2020: 22 · 2019: 15 · 2018: 10 · 2017: 5
FWCI: 9.92
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: GeroScience (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: SENS Research Foundation (BC2010)
National Institute on Aging (AG009909, AG017242)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Flavonoids in Medical Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
Health Sciences › Medicine › Biochemistry (medical) › Phytochemicals and Antioxidant Activities
Keywords: apigenin, senescence-associated secretory phenotype, cellular senescence, flavonoids, breast cancer, IRAK1, IRAK4, p38 MAPK, NF-κB, CXCL10, paracrine effects, replicative senescence, oncogenic Ras, MAPK signaling, extracellular matrix invasion, epithelial-mesenchymal transition, inflammation, aging
MeSH terms: Breast Neoplasms, Female, Fibroblasts, Humans, Phenotype, Signal Transduction, Interleukin-6, NF-kappa B, Cellular Senescence, Cell Culture Techniques, Apigenin, p38 Mitogen-Activated Protein Kinases, Cell Proliferation, Interleukin-1alpha, Interleukin-1 Receptor-Associated Kinases

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Apigenin suppresses the senescence-associated secretory phenotype and paracrine effects on breast cancer cells

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